Analgesic compositions



United States Patent Office 3,036,954 Patented May 29, 1962 3,036,954 ANALGESIC COMPOSITIONS Enos Brown Robbins, Indianapolis, Ind., assignor to Eli Lilly and Company, Indianapolis, Ind., a corporation of Indiana No Drawing. Filed Oct. 5, 1959, Ser. No. 844,173 3 Claims. (Cl. 167-65) This invention relates to novel analgesic compositions.

It is known that d-propoxyphene, identified chemically as a-d-LZ-diphenyl 2 propionoxy 3 methyl-4-dimethylaminobutane, is an efiiective analgesic agent. As such, it has been extensively used, generally in oral dosage form, for the relief of pain.

I have discovered that the analgesic activity of d-propoxyphene is enhanced and prolonged if there is combined with the d-propoxyphene an amount of phenaglycodol, 2- p-chlorophenyl-3-methyl-2,3-butanediol. The potentiation of the analgesic effectiveness of d-propoxyphene by means of pheuaglycodol is quite surprising since the latter compound is a tranquilizing agent with no observable analgesic activity. Furthermore, the amount of phenaglycodol required for the potentiation of the d-propoxyphene is less than the dose amount customarily used for tranquilizing response.

For etfective potentiation the phenaglycodol and dpropoxyphene are combined in a weight ratio upwards of about 3 parts of phenaglycodol to 1 part of d-propoxyphene. The presently preferred ratio is about 5 parts by weight of phenaglycodol to 1 part by weight of dpropoxyphene. A higher ratio, for example, a 7 to 1 ratio, can be employed, but ratios above this value are generally not desirable since the higher ratios provide an amount of phenaglycodol sufiicient to evoke a marked tranquilizing response. Although that elTect may be desirable in certain instances, such is not usually the case.

As is the case with therapeutic compositions of dpropoxyphene, the d-propoxyphene-phenaglycodol compositions of this invention can be employed in any of the usual therapeutic dosage forms such as filled capsules, compressed tablets, elixirs, suspensions, and the like. For reasons of convenience of administration and stability, filled capsules and compressed tablets are the preferred pharmaceutical forms, and such are readily compounded using the customary excipients and extending media.

The d-propoxyphene can be employed in the form of its free base, but generally is employed in the form of a nontoxic acid addition salt since the latter is more amenable to formulation.

If desired, other active therapeutic ingredients can be associated with the novel compositions of this invention, 'such ingredients generally being analgesic agents, for example, acetylsalicylic acid, acetophenetidine, codeine, and the like.

By virtue of the potentiating efiect of the phenaglycodol, the d-propoxyphene can be used a dose amount less than that customarily required. However, it is preferable to employ in my novel compositions the usual dose amount of d-propoxyphene, thereby to obtain a more pronounced analgesic action than is otherwise obtainable.

An illustrative composition suitable for filling into telescoping gelatin capsules is prepared by thoroughly mixing 1 part by weight of d-propoxyphene hydrochloride, 5 parts by weight of phenaglycodol, and 1.3 parts by weight of starch. The mixture is filled into telescoping gelatin capsules of such size that each capsule contains about 32 mg. of d-propoxyphene hydrochloride.

If desired, the foregoing composition can be made up to contain about 10 parts by weight of acetylsalicylic acid, in which case each 32 mg. dose of d-propoxyphene hydrochloride will provide about 320 mg. of acetylsalicylic acid.

An illustrative composition suitable for the preparation of compressed tablets is made up of the following ingredients in the amounts shown:

Parts by weight d-Propoxyphene hydrochloride 7 Phenaglycodol 35 M agnesium stearate 1 The d-propoxyphene hydrochloride and phenaglycodol and half the amounts of the starch and magnesium stearate are thoroughly mixed and are compressed into slugs. The slugs are sieved through a No. 12 screen. The remainder of the starch and magnesium stearate is then mixed with the screened material and the mixture is compressed on a standard tabletting machine into tablets of such size that each tablet contains about 32 mg. of d-propoxyphene hydrochloride.

I claim:

1. A therapeutic composition comprising about 1 part by weight of d-propoxyphene and from about 3 to about 7 parts by weight of phenaglycodol.

2. A therapeutic composition comprising about 1 part by weight of d-propoxyphene to about 5 parts by weight of phenaglycodol.

3. A therapeutic composition in dosage unit form comprising about 32 mg. of d-propoxyphene in the form of its hydrochloric acid addition salt and about mg. of phenaglycodol.

Starch powder References Cited in the file of this patent UNITED STATES PATENTS Pohland Dec. 27, 1955 OTHER REFERENCES 

1. A THERAPEUTIC COMPOSITION COMPRISING ABOUT 1 PART BY WEIGHT OF D-PROPOXYPHENE AND FROM ABOUT 3 TO ABOUT 7 PARTS BY WEIGHT OF PHENAGLYCODOL. 